nitrogen metabolism Flashcards
primary metabolites
needed for normal operation of metabolic pathways; amino acids, nucleotides, RNA, DNA, B vitamins
secondary metabolites
those organic compounds not needed for cell growth, development, or reproduction
alkaloids
plant-derived nitrogen-containing secondary metabolites; caffeine, morphine, taxol, LSD
fungal metabolites
penicillin, streptomycin, cyclosporin
nutritionally essential amino acids
PVT TIM HiLL ( phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, leucine, lysine)
conditionally essential amino acids
arginine, tyrosine, cysteine
Arginine
humans make arginine, but more is needed for unimpaired growth during childhood and pregnancy
tyrosine
becomes essential, whenver Phe is inadequate
cysteine
becomes essential, whenever Met is inadequate
why must diet be varied?
to get an adequate balance of AAs
what is low in essential amino acids?
vegetables and even animal proteins
how do omnivores gain advantage?
by eating both plant and animal protein
what are the sources of amino acids?
intracellular proteolysis, digestion of proteins in foodstuffs, de novo AA synthesis
intracellular proteolysis
removes misfolded as well as old and damaged proteins, supplies essential AAs when dietary intake is insufficient, controls cell-cycle transitions and cell disjunction
digestion of proteins in foodstuffs
supplies both nutritionally essential and nutritionally nonessential AAs
de novo AA synthesis
provides nutritionally nonessential AAs that are needed for protein synthesis; adjusts amino acid pools in different tissues, adjusts energy metabolism by controlling concentrations of central pathway metabolites; allows cells to adapt to metabolic stress; needed to make nucleotides, heme, hormones, as well as neurotransmitters
Intracellular protein turnover
turnover rate depends on metabolic state; greater protein degradation occurs whenever nitrogen intake is low because cells need essential amino acids to make vitally needed proteins
what are the three pathways for intracellular protein turnover?
lysosome pathway, proteasome pathway, autophagic pathway
lysosome pathway
lysosome is an acidic compartment where proteins are protonated and undergo partial unfolding due to repulsion, making them more susceptible to proteolysis
proteasome pathway
ubiquitin is a 8.6-kDa protein that is enzymatically joined to unfolded proteins, marking them for breakdown. only ubiquitinated proteins can enter proteasomes, barrel-like macromolecular structures that use on-board proteases to form small peptides and AAs
autophagic pathway
uses ubiquitin system and lysosomes to remove old organelles that are first engulfed in an autophagic vacuole
proteolysis
enzymatic cleavage of proteins
saliva (proteins)
low levels of proteases
stomach: low pH (proteins)
pepsin
small intestine; neutral pH (protein fragments)
fragments can’t refold at neutral pH; chymotrypsin, trypsin, carboxypeptidase, elastase
after getting through the proteins and protein fragments what are we left with?
mainly amino acids and di- and tri- peptides
zymogen activation
zymogen-> proteolytic cleavage-> active enzyme; inactive enzymes are safer to store; prevents autophagy and apoptosis
what are the 4 major digestive proteases?
pepsinogen, chymotrypsinogen, trypsinogen, procarboxypeptidase
pepsinogen
active enzyme=pepsin, optimally active at pH 1-3
chymotrypsinogen
active enzyme=chymotrypsin, optimally active at pH 7
trypsinogen
active enzyme: trypsin, optimally active at pH 7
procarboxypeptidase
active enzyme: carboxypeptidase, optimally active at pH 7
autocatalysis
any process in which a reaction product is capable of catalyzing its own formation
pepsinogen is formed in and released by ____________ cells, which store pepsinogen in ___________
gastric chief cells; secretory granules
once a few pepsin molecules are formed by acid catalysis…
they rapidly cleave many pepsinogen molecules, each forming considerably more molecules of catalytically active pepsin
what mediate catalysis at low pH for pepsin?
two active-site aspartyl residues
chymosin
acid protease that curds milk to hasten pepsin cleavage
what is NOT absorbed by healthy intestine?
dietary proteins; foreign proteins are immunogenic; must be proteolyzed to amino acids, di- &tri-peptides
proteolysis of protein foodstuffs process begins by making what?
zymogens; synthesized and stored in pancreas; secreted into small intestine-> only then converted to active catalysts
trysinogen activation
pancreas makes & stores trypsinogen in vesicles; secretory vesicles contain trysin inhibitor; prevents unwanted proteolysis of host cells; enterokinase converts trysinogen into trypsin; trypsin activates chymotrypsinogen to chymotrypsin
enterokinase
an ectoprotease on intestinal mucosal wall
pro-carboxypeptidase
activated to carboxypeptidase in a cleavage reaction that is catalyzed by trypsin
AAs and small peptides are…
actively transported (against the concentration gradient) into intenstinal brush border cells
amino acids and sodium ions are transported in the same direction, and transport is driven by…
transmembrane ion gradient (high na+ in intestinal lumen & low na+ in brush border)
cells use _____________ to drive Na+ outward and K+ inward
ATP-hydrolysis dependent pumps
what drives AA uptake?
cell’s chemiosmotic gradient
organs selectively import AAs they need thru…
organ-specific expression of AA-selective transporters
true nitrogen balance
intake=excretion
positive nitrogen balance
intake>excretion
negative nitrogen balance
intake<excretion
positive nitrogen balance is required for…
growth in childhood, growth in pregnancy, healing of wounds, convalescence
negative nitrogen balance occurs during…
starvation, malnutrition, disease (burns, trauma, surgery)
marasmus
malnutrition associated with extensive tissue and muscle wasting, with little/no edema
features: loose folds of skin hanging over buttocks
severe deficiency of nearly all nutrients, especially protein, carbohydrates, and lipids
protein-energy malfunction
resulting from inadequate intake of protein and calories
Kwashiorkor
translation: sickness last baby gets when the new baby arrives
acute childhood protein malnutrition
inadequate protein intake but adequate caloric intake
characteristics of kwashiorkor
irritability (neurotransmitter deficit), big belly (liver enlarged with fatty infiltrates) kids are always hungry & eat too much cassava (excess carbohydrate is stored as fat in liver), edema hypoalbuminemia causes osmotic imbalance within ankles, feet, and belly
